This invention relates to a method of controlling culture and an apparatus therefor. More particularly, it relates to a method of controlling culture and an apparatus therefor for the efficient production of metabolites such as antibiotics, amino acids, enzyme and physiologically active substances by microorganisms or animal or plant cells.
It has been a usual practice to produce the above-mentioned metabolite by microorganisms or animal or plant cells. Most of conventional processes have been carried out batchwise by simply culturing a seed culture in a medium in a culture tank, which would bring about a low productivity.
Thus the inventors have examined culture methods wherein substrate and inducer are added in the course of the cultivation to thereby improve the productivity. There has been reported no industrial studies about the stage of cultivation at which substrate and inducer should be added.
For example, Japanese Patent Laid-Open No. 141796/1983 has disclosed a culture method for the production of a metabolite, i.e. peptide. However, it is not possible to observe the growth of cells continuously, i.e. on-line, in this method. Thus, as a matter of course, the appropriate point for the addition of substrate and/or similar substances is not discussed therein. Japanese Patent Laid-Open No. 125686/1977 has disclosed a method for culture yeasts although it is not intended to produce metabolite. This method comprises feeding a culture broth depending on the total oxygen consumption rate while maintaining the so-called respiratory quotient within a definite range. Therefore a procedure comprising adding substrate(s) and/or similar substances while monitoring a change in the respiratory quotient is not adopted therein.